This project is to understand the processes used by the human T cell leukemia virus type 1 (HTLV-1)for the transformation of human cells. There are several concepts on how a cell can progress from normal physiology to achieve a transformed phenotype. To characterize transformation, we have studied cellular genetic integrity, cell cycle progression and the checkpoints within a cell that guard normal cellular division. We have studied several cellular proteins whose functions are perturbed by the HTLV-1 viral oncoprotein, Tax, during the course of cellular transformation. In the 2008 - 2009 period, we have made the following scientifc findings. 1) We have characterized a new Tax1-binding protein 1 (TAX1BP1) which is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation and whose activity is abrogated by Tax1. 2) We have profiled miRNA expression in HTLV-1-transformed human T-cell lines and primary peripheral blood mononuclear cells from adult T-cell leukemia patients. We have found two microRNAs that participate in the oncogenesis of HTLV-1 infected cells. 3) We have studied how Tax activates the pro-inflammatory factor NF-kappaB and how this activation is regulated by the prolyl isomerase Pin1 protein.